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Background: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs)., Objectives: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD., Methods: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy., Results: Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life., Conclusions: In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253)., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

This is an update from the report-Cardiac Drug and Psychotropic Drug Interactions: Significance and Recommendations-published in this journal in November-December 1999. As mentioned in that article there has been an explosion of new drugs both in psychiatry and cardiology without a sufficient understanding of their potential interactions. Also there is a need for methods to update drug interactions on an ongoing basis. This report describes: 1) examples of actual adverse interactions from clinical cases that move beyond some of the hypothesized contraindications included in the 2000 millennium publication; 2) confirmation of previous adverse interactions reported if they strengthen the earlier findings; 3) listing of new drugs, e.g., sildenafil (viagra) now commonly prescribed by psychiatrists and cardiologists; 4) reports explaining and/or refining mechanisms of adverse interactions; and 5) cautions and important associated phenomenon of either a cardiac or a psychotropic drug, e.g., valproic acid and cases of life-threatening pancreatitis. Methods of publicizing the new knowledge of cardiac drug-psychotropic drug interactions, e.g., the Internet and web sites are described.

Understanding cardiac drug interactions with concurrent psychotropic prescriptions is essential for the practicing cardiologist, primary care physician, and psychiatrist. There has been an explosion in the use of new drugs in both psychiatry and cardiology without widespread knowledge of their potential interactions. The increasing tendency toward polypharmacy, the use of psychotropic medications by cardiologists and primary care physicians caring for cardiac patients, and the growth of the aging population present major challenges for the practitioner. Finally, there is a need to have models and paradigms for predicting potential drug interactions-the cytochrome P450 schema. This article describes a method to identify, understand, and codify the interactions between psychotropic and cardiac drugs, a systematic approach for updating this key database, and specific cardiac-psychotropic drug interactions. Specifically, this paper 1) details the interactions, 2) addresses the level of their clinical significance, 3) describes the potential mechanism(s) of the interactions, and 4) offers recommendations to the clinician (Appendix). Because the majority of the original clinical trials, either for cardiac medications or for psychotropic drugs, did not include studies comparing these two drug domains contemporaneously, their interactions often become known only with their combined use in the clinical arena, using the patient as "guinea pig" and through subsequent reporting.

Understanding cardiac drug interactions with concurrent psychotropic prescriptions is essential for the practicing cardiologist and primary care physician, as well as for the psychiatrist. There has been an explosive use of new drugs in both psychiatry and cardiology without widespread knowledge of their potential interactions. The increasing tendency toward poly-pharmacy, the use of psychotropic medications by cardiologists and primary care physicians caring for cardiac patients, and the growth of the aging population present major challenges for the practitioner. Finally, there is a need to have models/paradigms for predicting potential drug interactions--e.g., the Cytochrome p450 schema. This paper describes a method to identify, understand, and codify the interactions between psychotropic and cardiac drugs, a systematic approach for updating this key database and specific cardiac-psychotropic drug interactions. Specifically, this paper 1) details the interactions, 2) addresses the level of their clinical significance, 3) describes the potential mechanism(s) of the interactions, and 4) offers recommendations to the clinician. Since the majority of the original clinical trials, either for cardiac medications or psychotropic drugs, do not include studies comparing these two drug domains contemporaneously, their interactions often become known only with their combined use in the clinical arena, using the patient as "guinea pig," and through subsequent reporting.